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Discovering translational biomarkers in neurodevelopmental disorders

Investment in drug development for neurodevelopmental disorders has suffered from recent failures in clinical trials that were based on promising preclinical findings. Here, we discuss development and validation of translational biomarkers of neurodevelopmental disorders that can enable more informative clinical experiments and translational success in these diseases.
  1. Mustafa Sahin

    1. Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.

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  2. Stephanie R. Jones

    1. Brown University and Alpert Medical School and Center for Neurorestoration and Neurotechnology, Providence, RI, USA.

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  3. John A. Sweeney

    1. University of Cincinnati, Cincinnati, OH, USA.

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  4. Elizabeth Berry-Kravis

    1. Rush University Medical Center, Chicago, IL, USA.

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  5. Barry W. Connors

    1. Brown University and Alpert Medical School, Providence, RI, USA.

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  6. Joshua B. Ewen

    1. Kennedy Krieger Institute; and Johns Hopkins University, Baltimore, MD, USA.

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  7. Adam L. Hartman

    1. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

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  8. April R. Levin

    1. Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.

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  9. William Z. Potter

    1. National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

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  10. Laura A. Mamounas

    1. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

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Neurodevelopmental disorders (NDDs) are heterogeneous childhood-onset conditions that result from disrupted brain development and functioning. In the US, approximately one in six children are diagnosed with an NDD. Direct and indirect health-care costs associated with these disorders are substantial, and the lifetime cost of raising a child with autism spectrum disorder (ASD) and intellectual disability is estimated at $2.4 million in the US and £1.5 million in the UK.

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Nature Reviews Drug Discovery 18, 235-236 (2019)

doi: https://doi.org/10.1038/d41573-018-00010-7

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Supplementary Information

  1. Sahin-S1

Competing Interests

• Mustafa Sahin reports grant support from Novartis, Roche, Pfizer, Ipsen, LAM Therapeutics and Quadrant Biosciences. He has served on scientific advisory boards for Sage, Roche and Takeda.

• Elizabeth Berry-Kravis has been a consultant for Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin and Ovid Pharmaceuticals; a consultant for Novartis, Roche and Neurotrope regarding the conduct of clinical trials in fragile X syndrome (FXS) and other rare neurological diseases; on the scientific advisory board for Vteese/Mallinckrodt to provide guidance on clinical trials in Niemann–Pick type C (NP-C) disease; and has received research funding to conduct clinical trials in FXS and/or other neurodevelopmental disorders from Novartis, Roche, Seaside Therapeutics, Alcobra and Neuren, from Ovid and Zynerba to conduct a clinical trial in NP-C, from Vtesse/Mallinckrodt and from Asuragen to develop fragile X mental retardation 1 testing standards.

• William Z. Potter has served on advisory boards to Eli Lilly, Takeda, Astellas, Praxis and Noven and holds Merck & Co. stock.

• Arthur Combs is an employee and officer of MC10.

• Lauren Ethridge has served as a consultant to Ovid, Fulcrum and Novartis for work in FXS and Phelan McDermid syndrome.

• André Fenton is a founder of Bio-Signal Group Corp.

• Flavio Frohlich is the lead inventor of intellectual property (IP) filed by the University of North Carolina. The clinical studies performed in the Frohlich Lab have originally received a designation as conflict of interest with administrative considerations that was subsequently removed. Frohlich is the founder, chief scientific officer and majority owner of Pulvinar Neuro LLC. The company played no role in this workshop. Flavio Frohlich is also an author with Elsevier and receives royalty payments.

• David R. Hessl has served as a consultant to Ovid and Zynerba regarding FXS clinical trials.

• Shafali S. Jeste has served as a consultant to Roche.

• Darcy A. Krueger has received consulting fees from Novartis and Upsher-Smith and additional research support from Novartis.

• Gregory Light has been a consultant to Astellas, Boehringer Ingelheim, Dart NeuroScience, Heptares, Lundbeck, Merck & Co. , NeuroSig and Takeda.

• Eric Marsh has been a site principal investigator for studies from GW Pharma, Neuren, Zogenix, Ovid and Marinus.

• Matthew W. Mosconi has served as a consultant on an investigator-initiated study of Phelan McDermid syndrome supported by Novartis.

• Declan Murphy has served on an advisory board to Roche.

• Gahan Pandina is an employee of Janssen Research & Development and is a Johnson & Johnson stockholder.

• Joseph Piven is the editor of the Journal of Neurodevelopmental Disorders, Springer Nature.

• Alexander Rotenberg has received research support from Brainsway, CREmedical, Nexstim, Neuroelectrics, Roche, Sage and Takeda.

• Timothy Roberts has been on consulting and /or advisory board positions with CTF, Ricoh and Spago, has IP licensing arrangements with MEGIN and has stock options in Prism Clinical Imaging

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